Microenvironment-regulated dual-hydrophilic coatings for glaucoma valve surface engineering.

Glaucoma valves (GVs) play an essential role in treating glaucoma. However, fibrosis after implantation has limited their long-term success in clinical applications. In this study, we aimed to develop a comprehensive surface-engineering strategy to improve the biocompatibility of GVs by constructing a microenvironment-regulated and dual-hydrophilic antifouling coating on a GV material (silicone rubber, SR). The coating was based on a superhydrophilic polydopamine (SPD) coating with good short-range superhydrophilicity and antifouling abilities. In addition, SPD coatings contain many phenolic hydroxyl groups that can effectively resist oxidative stress and the inflammatory microenvironment. Furthermore, based on its in situ photocatalytic free-radical polymerization properties, the SPD coating polymerized poly 2-methylacryloxyethylphosphocholine, providing an additional long-range hydrophilic and antifouling effect. The in vitro test results showed that the microenvironment-regulated and dual-hydrophilic coatings had anti-protein contamination, anti-oxidation, anti-inflammation, and anti-fiber proliferation capabilities. The in vivo test results indicated that this coating substantially reduced the fiber encapsulation formation of the SR material by inhibiting inflammation and fibrosis. This design strategy for dual hydrophilic coatings with microenvironmental regulation can provide a valuable reference for the surface engineering design of novel medical implantable devices. STATEMENT OF SIGNIFICANCE: Superhydrophilic polydopamine (SPD) coatings were prepared on silicone rubber (SR) by a two-electron oxidation method. Introduction of pMPC to SPD surface using photocatalytic radical polymerization to obtain a dual-hydrophilic coating. The dual-hydrophilic coating effectively modulates the oxidative and inflammatory microenvironment. This coating significantly reduced protein contamination and adhesion of inflammatory cells and fibroblasts in vitro. The coating-modified SR inhibits inflammatory and fibrosis responses in vivo, promising to serve the glaucoma valves.

Value of q waves in lateral and left precordial leads in patients with left bundle branch block to predict the response to cardiac resynchronization therapy.

BACKGROUND: The cardiac resynchronization therapy (CRT) non-response rate can reach 30% in heart failure (HF) patients with left bundle branch block (LBBB). This study aimed to evaluate the value of baseline q waves in leads I, V5, or V6 in predicting response to CRT in patients with HF and LBBB. METHODS: Patients with HF (left ventricular ejection fraction ≤35%) and LBBB receiving CRT implantation were retrospectively enrolled. Baseline characteristics and electrocardiogram parameters, including lateral and left precordial q waves were evaluated. Non-response to CRT was defined as the improvement of left ventricular ejection fraction (LVEF) < 5% at a 6-month follow-up. RESULTS: A total of 132 patients (mean age 63.0 ± 10.4 years, 94 [71.2%] male) were included. Among them, 32 patients with q waves in leads I, V5, or V6 were classified into the qLBBB (+) group, and the rest without q waves in these leads were defined as the qLBBB (-) group. The CRT non-response rate in the qLBBB (+) group was markedly higher than that in the qLBBB (-) group (68.8% vs. 33.3%, p < .001). Multivariable logistic regression analysis revealed that the presence of baseline q waves in leads I, V5, or V6 remained significantly associated with a higher rate of CRT non-response in patients with HF and LBBB (odds ratio: 4.8, 95% confidence interval: 1.5-15.0, p = .007). CONCLUSION: Any q wave in leads I, V5, or V6 was an independent predictive factor for CRT non-response in patients with HF and LBBB.

A new species of Neohydatothrips (Thysanoptera: Sericothripinae) from China.

Neohydatothrips stachyurus sp. n. is described from Guizhou, China. Morphologically, this new Sericothripinae species is characterized by the shape of blotch on pronotum and the distribution of microtrichia on abdominal segments. The distribution of Neohydatothrips species from China also is discussed.

TRPM7 kinase activity induces amyloid-ß degradation to reverse synaptic and cognitive deficits in mouse models of Alzheimer's disease.

Altered abundance or activity of the dual-function transient receptor potential melastatin-like 7 (TRPM7) protein is implicated in neurodegenerative disorders, including Alzheimer's disease (AD). Toxic aggregation of amyloid-ß (Aß) in neurons is implicated in AD pathology. Here, we found that the kinase activity of TRPM7 is important to stimulate the degradation of Aß. TRPM7 expression was decreased in hippocampal tissue samples from patients with AD and two mouse models of AD (APP/PS1 and 5XFAD). In cultures of hippocampal neurons from mice, overexpression of full-length TRPM7 or of its functional kinase domain M7CK prevented synapse loss induced by exogenous Aß. In contrast, this neuroprotection was not afforded by overexpression of either the functional ion channel portion alone or a TRPM7 mutant lacking kinase activity. M7CK overexpression in the hippocampus of young and old 5XFAD mice prevented and reversed, respectively, memory deficits, synapse loss, and Aß plaque accumulation. In both neurons and mice, M7CK interacted with and activated the metalloprotease MMP14 to promote Aß degradation. Thus, TRPM7 loss in patients with AD may contribute to the associated Aß pathology.

Oriented Zinc Metal Anode Based on Directional Recognition and Assembly.

The practical application of aqueous zinc batteries are highly limited by unsatisfied Zn anodes for the unavoidable dendrite growth and side reactions. Crystal orientation engineering is an effective way to overcome these inherent drawbacks. However, how to achieve Zn plating with manipulated crystallographic orientation is still a great challenge. Herein, a uniform (002)-oriented Zn metal anode is reported based on a directional cation recognition and crystal assembly strategy. The activated layered double hydroxide (Act-LDH) exhibits favorable adsorption energy with Zn2+ and high lattice matching with Zn (002) plane, which can be served as directional recognition layer to anchor Zn2+ and regulate crystallographic orientation of Zn as well. As demonstration, Zn crystals with ultrahigh ratio of (002)/(100) plane of 15.7 are assembled parallelly on horizontal Act-LDH, in which high CE of 99.85% maintains over 18 000 cycles. The symmetric battery with (002)-oriented Zn shows stable plating/stripping process over 1650 and 420 h at 1 mA cm-2 /0.5 mA h cm-2 and 10 mA cm-2 /5 mA h cm-2 , respectively, which is 9 and 12 times higher than unoriented polycrystalline Zn. Moreover, as-assembled full battery displays high specific capacity of 120 mA h g-1 at 2 A g-1 over 1800 cycles.

Genetic Diversity and Fine-Scale Genetic Structure of Spodoptera litura Fabricius (Lepidoptera: Noctuidae) in Southern China Based on Microsatellite Markers.

Population genetic structure is strongly affected by dispersal events, especially for migratory species. The investigation of population structure is therefore conducive to increasing our understanding of species dispersal. Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is an important tobacco pest in China causing serious damage to multiple crops. In this study, we explore its dispersal dynamics by clarifying the fine-scale population genetics using 545 S. litura samples collected from tobacco plantations at 24 locations (mainly in Baise, Hechi, and Hezhou, Southern China). We analyzed the genetic diversity, genetic structure, and gene flow of these populations using seven microsatellite loci. Our results revealed high genetic diversity and low population genetic structure among S. litura. The genetic distance was uncorrelated with geographical distance, indicating the complete randomness of dispersal among the local populations. Our results suggest that the movement scope of contemporary S. litura might be much higher than the local-level spatial scale, which will provide a theoretical basis for pest management.

The Food and Drug Administration-approved antipsychotic drug trifluoperazine, a calmodulin antagonist, inhibits viral replication through PERK-eIF2α axis.

Virus-related diseases are seriously threatening human health, but there are currently only 10 viruses with clinically approved antiviral drugs available. As non-cellular organisms, viruses parasitize in living cells and rely on the protein synthesis mechanism of the host cells. In this study, we found that the antipsychotic drug trifluoperazine (TFP), a dual dopamine receptor D2 (DRD2)/calmodulin (CALM) antagonist, increases the phosphorylation of eukaryotic initiation factor 2α (eIF2α), a key factor in the regulation of protein synthesis and significantly inhibits vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) replication. CALM but not DRD2 is involved in the antiviral activity of TFP. By knockdown of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) we found that the antiviral function of TFP is dependent on PERK, a stress response kinase that mediates eIF2α phosphorylation. Furthermore, the results of animal experiments showed that TFP protects mice from lethal VSV attacks, improving the survival rate and reducing lung injury. Taken together, these data suggests that TFP inhibits virus replication through PERK-eIF2α axis, and this broad-spectrum of mechanisms are worth further evaluation in clinical trials in the future.

Screening for Atrial Fibrillation by Village Doctors in Rural Areas of China: The Jiangsu Province Rural Community AF Project.

China has a large population of elderly in rural areas. Village doctors are acting as health-care gatekeepers for the rural elderly in China and are encouraged to provide more long-term care for patients with chronic diseases such as atrial fibrillation (AF). The data of AF registries from the rural elderly are limited. The present registry aims to provide contemporary data on the current AF-related health status of the rural elderly and the gaps in management of AF by village doctors. This study has two phases. The first phase is a cross-sectional study of AF screening in two rural towns of eastern China. All the residents aged ≥65 years are eligible and will be invited to attend a government-led health examination or an in-house AF screening program. The AF detection rate, the awareness of AF and the usage of oral anticoagulants and smartphones by AF patients, and the ability to diagnose and manage AF by village doctors will be assessed. Participants with AF detected in the first phase are eligible for the second phase. A variety of modes of intensified education will be provided to all AF patients and their family members to enrich their AF-related knowledge. Their village doctors will be offered a lecture-based training program focusing on Atrial fibrillation Better Care (ABC) pathway. Follow-up will be conducted for 1 year. The primary endpoint is the composite of all stroke and all-cause mortality. The first phase of AF screening was conducted between April 2019 and June 2019, and 18,712 participants with the mean age of 73.1±5.8 years were enrolled. The second phase that includes 810 patients with AF, started on 1 May 2019. This study will provide a perspective of primary care system and would indirectly reflect the current status of chronic disease care in rural China.

Trimetazidine inhibits liver fibrosis and hepatic stellate cell proliferation and blocks transforming growth factor-ß (TGFß)/Smad signaling in vitro and in vivo.

Trimetazidine (TMZ) has been used extensively to treat coronary artery disease and to reduce fibrosis. Liver fibrosis is a reversible process. However, the impacts of TMZ on liver fibrosis triggered by CCl4 and on hepatic stellate cells in liver fibrosis remain to be elaborated. In the current study, the liver fibrosis models were constructed by using CCl4-induced mice and TGF-ß-induced hepatic stellate cells. The involvement of TMZ in liver fibrosis was subsequently investigated. In the CCl4-induced hepatic fibrosis mouse model, it was shown that the expression levels of alanine aminotransferase and aspartate aminotransferase were reduced after TMZ treatment; the expression levels of the extracellular matrix proteins colla1 and α-SMA were down-regulated; furthermore, the expression levels of TGFß/Smad signaling proteins were inhibited. In TGF-ß-induced hepatic stellate cells, compared to the TGF-ß-induced group, cell proliferation and migration were inhibited after TMZ treatment; meanwhile, extracellular matrix protein and TGFß/Smad signaling protein expression levels followed the same trend as in the hepatic fibrosis model. In conclusion, TMZ could block the TGFß/Smad signaling in liver fibrosis model, with inhibiting liver fibrosis and hepatic stellate cell proliferation. This may broaden the application sphere of TMZ in liver fibrosis therapy.

LongShengZhi alleviated cardiac remodeling via upregulation microRNA-150-5p with matrix metalloproteinase 14 as the target.

ETHNOPHARMACOLOGICAL RELEVANCE: LongShengZhi capsule (LSZ), a traditional Chinese medicine, is used for treatment of patients with vascular diseases. LSZ reduced doxorubicin-induced heart failure by reducing production of reactive oxygen species and inhibiting inflammation and apoptosis. AIM OF THE STUDY: This study was to explore whether LSZ could alleviate cardiac remodeling via upregulation of microRNA (miR)-150-5p and the downstream target. Cardiac remodeling was induced by Ang II in vivo and in vitro. RESULTS: LSZ attenuated Ang II-induced cardiac hypertrophy and fibrosis in rats, and in primary cardiomyocytes (CMs) and primary cardiac fibroblasts (CFs). MiR-150-5p was downregulated in Ang II-induced rat heart, CMs and CFs, and these decreases were reserved by LSZ. In vivo overexpression of miR-150-5p by transfection of miR-150-5p agomiR protected Ang II-induced cardiac hypertrophy and fibrosis in rats. Meanwhile, its overexpression also reversed Ang II-induced upregulation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC) in rat hearts and primary CMs, as well as upregulation of collagen I, collagen III and transforming growth factor-ß (TGF-ß) in rat hearts and primary CFs. Matrix metalloproteinase 14 (MMP14) was validated as the target gene of miR-150-5p, which was overexpressed in Ang II-induced rat heart, rat primary CMs and primary CFs. Notably, overexpression of MMP14 induced cardiac remodeling, and reversed the protective role of miR-150-5p in downregulating Ang II-induced upregulation of hypertrophy and fibrosis markers in vitro. CONCLUSION: Collectively, LSZ protects Ang II-induced cardiac dysfunction and remodeling via upregulation of miR-150-5p to target MMP14. Administration of LSZ, upregulation of miR-150-5p or targeting of MMP14 may be strategies for cardiac remodeling therapy.

Regulation of Intrinsic and Bystander T Follicular Helper Cell Differentiation and Autoimmunity by Tsc1.

T Follicular helper (Tfh) cells promote germinal center (GC) B cell responses to develop effective humoral immunity against pathogens. However, dysregulated Tfh cells can also trigger autoantibody production and the development of autoimmune diseases. We report here that Tsc1, a regulator for mTOR signaling, plays differential roles in Tfh cell/GC B cell responses in the steady state and in immune responses to antigen immunization. In the steady state, Tsc1 in T cells intrinsically suppresses spontaneous GC-Tfh cell differentiation and subsequent GC-B cell formation and autoantibody production. In immune responses to antigen immunization, Tsc1 in T cells is required for efficient GC-Tfh cell expansion, GC-B cell induction, and antigen-specific antibody responses, at least in part via promoting GC-Tfh cell mitochondrial integrity and survival. Interestingly, in mixed bone marrow chimeric mice reconstituted with both wild-type and T cell-specific Tsc1-deficient bone marrow cells, Tsc1 deficiency leads to enhanced GC-Tfh cell differentiation of wild-type CD4 T cells and increased accumulation of wild-type T regulatory cells and T follicular regulatory cells. Such bystander GC-Tfh cell differentiation suggests a potential mechanism that could trigger self-reactive GC-Tfh cell/GC responses and autoimmunity via neighboring GC-Tfh cells.

ß-Arrestin 2 Regulates Inflammatory Responses against Mycobacterium tuberculosis Infection through ERK1/2 Signaling.

Mycobacterium tuberculosis, the pathogen that causes tuberculosis, exhibits complex host-pathogen interactions. Pattern recognition receptors and their downstream signaling pathways play crucial roles in determining the outcome of infection. In particular, the scaffold protein ß-arrestin 2 mediates downstream signaling of G protein-coupled receptors. However, the role of ß-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that ß-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis infection upregulated ß-arrestin 2 expression in human macrophages, and silencing of ß-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-α. ß-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis infection. Furthermore, ß-arrestin 2 transcriptionally regulates TNF-α by binding to CREB1. These observations revealed that the upregulation of ß-arrestin 2 is critical for M. tuberculosis to escape immune surveillance through an unknown mechanism. Our research offers a novel interference modality to enhance the immune response against tuberculosis by targeting ß-arrestin 2 to modulate the TLR2-ß-arrestin 2-ERK1/2-CREB1-TNF-α regulatory axis.

Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.

Mucosal-associated invariant T (MAIT) cells have important functions in immune responses against pathogens and in diseases, but mechanisms controlling MAIT cell development and effector lineage differentiation remain unclear. Here, we report that IL-2/IL-15 receptor ß chain and inducible costimulatory (ICOS) not only serve as lineage-specific markers for IFN-γ-producing MAIT1 and IL-17A-producing MAIT17 cells, but are also important for their differentiation, respectively. Both IL-2 and IL-15 induce mTOR activation, T-bet upregulation, and subsequent MAIT cell, especially MAIT1 cell, expansion. By contrast, IL-1ß induces more MAIT17 than MAIT1 cells, while IL-23 alone promotes MAIT17 cell proliferation and survival, but synergizes with IL-1ß to induce strong MAIT17 cell expansion in an mTOR-dependent manner. Moreover, mTOR is dispensable for early MAIT cell development, yet pivotal for MAIT cell effector differentiation. Our results thus show that mTORC2 integrates signals from ICOS and IL-1ßR/IL-23R to exert a crucial role for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.

Long Noncoding RNA LINC00963 Promotes CDC5L-Mediated Malignant Progression in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is a common cancer with high incidence and mortality worldwide. In recent years, accumulating evidence has shown that long noncoding RNAs (lncRNAs) exert critical roles in the development and progression of cancer by acting as a tumor initiator or suppressor. LINC00963 is a newly reported lncRNA related to cancer, and its role in GC remains unclear. MATERIALS AND METHODS: The expression levels of LINC00963, miR-612, and cell division cycle 5-like protein (CDC5L) were measured using quantitative real-time PCR or Western blot. The biological functions of LINC00963, miR-612, and CDC5L in GC cells were analyzed by transwell and proliferation experiments. The expression of CDC5L in patients with GC was evaluated using the Oncomine database. Bone marrow-derived dendritic cells (DCs) were derived from C57BL/6 mice. RESULTS: LINC00963 expression was higher in GC tissues than in adjacent normal tissues. Similar results were found in GC cell lines and normal human gastric epithelial cells. Upregulation of LINC00963 was related to the poor prognosis of patients with GC. Knockdown of LINC00963 inhibited the proliferation, invasion, and metastasis but promoted the apoptosis of GC cells. Furthermore, silencing of LINC00963 in GC cells significantly suppressed the tumor growth of GC. Bioinformatics analysis indicated that LINC00963 could target miR-612 by functioning as a competing endogenous RNA. The expression of miR-612 decreased in GC tissues and cell lines. Meanwhile, LINC00963 expression was negatively associated with miR-612. CDC5L was a direct target of miR-612. miR-612 suppressed the expression of CDC5L in GC tissues and cells. Moreover, LINC00963 inhibited the differentiation and maturation of DCs by regulating miR-612 expression in DCs. CONCLUSION: LINC00963 promoted the progression of GC by competitively binding to miR-612 to regulate the expression of CDC5L and mediated DC-related anti-tumor immune response. Thus, targeting LINC00963 may be a promising therapeutic strategy for GC.

Coordinating Adsorption and Catalytic Activity of Polysulfide on Hierarchical Integrated Electrodes for High-Performance Flexible Li-S Batteries.

Lithium-sulfur (Li-S) batteries have been known to be a promising substitute because of their much higher theoretical energy density than that of traditional Li-ion batteries. However, the low utilization of sulfur caused by the poor conductivity of sulfur and shuttle of lithium polysulfides (LiPSs) severely restrict the commercial application of Li-S batteries, especially in flexible wearable devices. Herein, a hierarchical nitrogen-doped carbon nanotube (NCNT)@Co-Co3O4 nanowire array (NWA)-integrated electrode was developed based on the rational design of density functional theory calculations, which shows simultaneous confinement adsorption and catalysis conversion of LiPSs. In situ Raman spectra further proved that the NCNT@Co-Co3O4 NWAs exhibit sufficient adsorption capacity and high catalytic conversion of LiPSs. As a result, the NCNT@Co-Co3O4@S electrode exhibited the desirable specific capacity and excellent cyclic stability at both low and high sulfur loadings. Moreover, pouch cells with the NCNT@Co-Co3O4@S cathode show higher capacity under flat or bending states and longer cycle stability than that of the reported results. This work provides a new approach for the development of high-performance Li-S batteries toward future wearable electronics.

Tumor Microenvironmental Responsive Liposomes Simultaneously Encapsulating Biological and Chemotherapeutic Drugs for Enhancing Antitumor Efficacy of NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most lethal types of cancer with highly infiltrating. Chemotherapy is far from satisfactory, vasculogenic mimicry (VM) and angiogenesis results in invasion, migration and relapse. PURPOSE: The objective of this study was to construct a novel CPP (mmp) modified vinorelbine and dioscin liposomes by two new functional materials, DSPE-PEG2000-MAL and CPP-PVGLIG-PEG5000, to destroy VM channels, angiogenesis, EMT and inhibit invasion and migration. METHODS AND RESULTS: The targeting liposomes could be enriched in tumor sites through passive targeting, and the positively charged CPP was exposed and enhanced active targeting via electrostatic adsorption after being hydrolyzed by MMP2 enzymes overexpressed in the tumor microenvironment. We found that CPP (mmp) modified vinorelbine and dioscin liposomes with the ideal physicochemical properties and exhibited enhanced cellular uptake. In vitro and in vivo results showed that CPP (mmp) modified vinorelbine and dioscin liposomes could inhibit migration and invasion of A549 cells, destroy VM channels formation and angiogenesis, and block the EMT process. Pharmacodynamic studies showed that the targeting liposomes had obvious accumulations in tumor sites and magnificent antitumor efficiency. CONCLUSION: CPP (mmp) modified vinorelbine plus dioscin liposomes could provide a new strategy for NSCLC.

TIP60 K430 SUMOylation attenuates its interaction with DNA-PKcs in S-phase cells: Facilitating homologous recombination and emerging target for cancer therapy.

Nonhomologous end joining (NHEJ) and homologous recombination (HR) are major repair pathways of DNA double-strand breaks (DSBs). The pathway choice of HR and NHEJ is tightly regulated in cellular response to DNA damage. Here, we demonstrate that the interaction of TIP60 with DNA-PKcs is attenuated specifically in S phase, which facilitates HR pathway activation. SUMO2 modification of TIP60 K430 mediated by PISA4 E3 ligase blocks its interaction with DNA-PKcs, whereas TIP60 K430R mutation recovers its interaction with DNA-PKcs, which results in abnormally increased phosphorylation of DNA-PKcs S2056 in S phase and marked inhibition of HR efficiency, but barely affects NHEJ activity. TIP60 K430R mutant cancer cells are more sensitive to radiation and PARP inhibitors in cancer cell killing and tumor growth inhibition. Collectively, coordinated regulation of TIP60 and DNA-PKcs facilitates HR pathway choice in S-phase cells. TIP60 K430R mutant is a potential target of radiation and PARPi cancer therapy.

Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.

Diacylglycerol kinases (DGKs) play important roles in restraining diacylglycerol (DAG)-mediated signaling. Within the DGK family, the ζ isoform appears to be the most important isoform in T cells for controlling their development and function. DGKζ has been demonstrated to regulate T cell maturation, activation, anergy, effector/memory differentiation, defense against microbial infection, and antitumor immunity. Given its critical functions, DGKζ function should be tightly regulated to ensure proper signal transduction; however, mechanisms that control DGKζ function are still poorly understood. We report here that DGKζ dynamically translocates from the cytosol into the nuclei in T cells after TCR stimulation. In mice, DGKζ mutant defective in nuclear localization displayed enhanced ability to inhibit TCR-induced DAG-mediated signaling in primary T cells, maturation of conventional αßT and iNKT cells, and activation of peripheral T cells compared with WT DGKζ. Our study reveals for the first time nuclear sequestration of DGKζ as a negative control mechanism to spatially restrain it from terminating DAG mediated signaling in T cells. Our data suggest that manipulation of DGKζ nucleus-cytosol shuttling as a novel strategy to modulate DGKζ activity and immune responses for treatment of autoimmune diseases and cancer.

Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice.

Mucosal-associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRVα19-Jα33 (iVα19) TCR, which triggers signals crucial for their development. However, signal pathways downstream of the iVα19TCR and their regulation in MAIT cells are unknown. Diacylglycerol (DAG) is a critical second messenger that relays the TCR signal to multiple downstream signaling cascades. DAG is terminated by DAG kinase (DGK)-mediated phosphorylation and conversion to phosphatidic acid. We have demonstrated here that downregulation of DAG caused by enhanced DGK activity impairs late-stage MAIT cell maturation in both thymus and spleen. Moreover, deficiency of DGKζ but not DGKα by itself causes modest decreases in MAIT cells, and deficiency of both DGKα and ζ results in severe reductions of MAIT cells in an autonomous manner. Our studies have revealed that DAG signaling is not only critical but also must be tightly regulated by DGKs for MAIT cell development and that both DGKα and, more prominently, DGKζ contribute to the overall DGK activity for MAIT cell development.

Sub-family relationships of Bradinothrips Hood and Parascolothrips Mound (Thysanoptera, Thripidae).

A cladistic analysis based on 31 morphological characters of female adults recovered two genera currently placed in subfamily Thripinae, Bradinothrips Hood and Parascolothrips Mound, as closely related to two Panchaetothripinae genera, Monilothrips Moulton and Zaniothrips Bhatti. Thus, following the results of this analysis, we propose the transference of the first two genera to subfamily Panchaetothripinae, under the tribe Monilothripini.